Surgical Stress Promotes Tumor Growth in Ovarian Carcinoma

被引：170

作者：

Lee, Jeong-Won ^{[1
,4
]}

Shahzad, Mian M. K. ^{[1
,3
]}

Lin, Yvonne G. ^{[1
]}

Armaiz-Pena, Guillermo ^{[1
]}

Mangala, Lingegowda S. ^{[1
]}

Han, Hee-Dong ^{[1
]}

Kim, Hye-Sun ^{[1
,5
,6
]}

Nam, Eun Ji ^{[1
,7
]}

Jennings, Nicholas B. ^{[1
]}

Halder, Jyotsnabaran ^{[1
]}

Nick, Alpa M. ^{[1
]}

Stone, Rebecca L. ^{[1
]}

Lu, Chunhua ^{[1
]}

Lutgendorf, Susan K. ^{[8
]}

Cole, Steve W. ^{[9
]}

Lokshin, Anna E. ^{[10
]}

Sood, Anil K. ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA

[4] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea

[5] Kwandong Univ, Coll Med, Cheil Gen Hosp, Dept Pathol, Kangnung, South Korea

[6] Kwandong Univ, Coll Med, Womens Healthcare Ctr, Kangnung, South Korea

[7] Yonsei Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea

[8] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA

[9] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90024 USA

[10] Univ Pittsburgh, Dept Pathol & Med, Pittsburgh, PA USA

来源：

CLINICAL CANCER RESEARCH | 2009年 / 15卷 / 08期

关键词：

AWAKE EPIDURAL-ANESTHESIA; KILLER-CELL CYTOTOXICITY; INTERFERING RNA DELIVERY; METASTATIC COLONIZATION; DEPENDENT MECHANISM; SURGERY; CANCER; ANGIOGENESIS; LAPAROTOMY; RESECTION;

D O I：

10.1158/1078-0432.CCR-08-2966

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Surgical stress has been suggested to facilitate the growth of preexisting micrometastases as well as small residual tumor postoperatively. The purpose of this study was to examine the effects of surgical stress on ovarian cancer growth and to determine underlying mechanisms responsible for increased growth. Experimental Design: To mimic the effects of surgery, we did a laparotomy or mastectomy under isoflurane inhalation on athymic nude mice 4 days after i.p. tumor cell injection. Propranolol infusion via Alzet pumps was used to block the influence of sympathetic nervous system activation by surgical stress. Results: In both HeyA8 and SKOV3ip1 models, the mice in the laparotomy and mastectomy groups had significantly greater tumor weight (P < 0.05) and nodules (P < 0.05) compared with anesthesia only controls. There was no increase in tumor weight following surgery in the beta-adrenergic receptor-negative RMG-II model. Propranolol completely blocked the effects of surgical stress on tumor growth, indicating a critical role for beta-adrenergic receptor signaling in mediating the effects of surgical stress on tumor growth. In the HeyA8 and SKOV3ip1 models, surgery significantly increased microvessel density (CD31) and vascular endothelial growth factor expression, which were blocked by propranolol treatment. Conclusion: These results indicate that surgical stress could enhance tumor growth and angiogenesis, and beta-blockacle might be effective in preventing such effects.

引用

页码：2695 / 2702

页数：8

共 35 条

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